Determination by the immune system of chemo- and immunotherapy of a murine tumor was investigated. The effect of cyclophosphamide and levan (polyfructose) in single and combined treatment on the growth of the F10 variant of B16 melanoma was tested in splenectomized and non-splenectomized mice. Splenectomy was found to increase markedly the efficiency of all treatments, particularly the combined treatment, as judged by the delay of appearance and size of the subcutaneous tumors at the site of inoculation. Nevertheless, mortality rate was not always in correlation with the rate of local tumor evolution: some of the treated splenectomized mice died earlier than expected, with relatively small local tumors, due to enhanced metastasis. The results indicate that elements in the spleen of C57BL mice decrease the therapeutic efficiency of the drugs tested. It can be deduced that splenectomy must not be considered to increase the risk of a tumor-bearing host in all cases. On the contrary, it may improve the efficiency of cancer treatment in certain tumor-host systems.